托法替布及其光学异构体的NP-HPLC法分离与测定

Separation and Determination of Tofacitinib and Its Optical Isomers by NP-HPLC

建立了正相高效液相色谱法分离托法替布及其光学异构体,并定量测定其对映异构体和非对映异构体。采用Chiralpak AS-H手性柱,以正己烷∶乙醇∶甲醇∶乙醇胺（70∶20∶10∶0.2）为流动相,检测波长290 nm。托法替布及其光学异构体均分离完全。3R,4S-型、3S,4R-型非对映异构体和3S,4S-型对映异构体分别在0.6~12、0.6~12和0.5~10μg/ml范围内线性关系良好;平均回收率分别为100.8%、98.8%和98.6%,RSD分别为1.21%、1.34%和1.61%。

An NP-HPLC method was established for the chiral separation of tofacitinib and its optical isomers, as well as the determination of the enantiomer and diastereoisomers. A Chiralpak AS-H column was used, with the mobile phase of hexane ： ethanol ： methanol ：2-aminoethanol （70 ：20 ：10 ：0.2） at the detection wavelength of 290 nm. Tofacitinib and its optical isomers could be separated completely. Their were linear for the （3R,4S）- and （3S,4R）- diastereoisomers and （3S,4S） - enantiomer in the ranges of 0.6-12, 0.6-2 and 0.5-10 μg/ml, respectively. The average recoveries of diastereoisomers and enantiomer were 100.8 %, 98.8 % and 98.6 %, with RSDs of 1.21%, 1.34 % and 1.61%, respectively.